The subject of this study is the neurogenic influences that affect the metabolism of mammalian skeletal muscle. It is known that innervation is critical for the induction of metabolic specialization of muscle cells and for the maintenance of that specialization. The mechanism by which nerve acts and its influence over myogenic properties are poorly understood. The proposed study is to investigate the hypothesis that the role of nerve in regulating muscle biochemicstry is mediated primarily by the contractile activity it imposes rather than by putative chemical substances or nerve-muscle contact. Regulation will be assessed by measuring enzymes characterizing the major metabolic muscle fiber types. The unique feature of this study is the comprehensive use of microanalytical biochemistry due to heterogeneity of metabolic properties among fibers. The influence of contractile activity on levels of metabolic enzymes will be examined under the following general topics: 1) Cell type differentiation will be followed in culture, with or without contractile activity; 2) Fiber type plasticity of mature cells will be tested in vivo with new patterns of contractile activity following reinnervation, and following artifical stimulation; 3) Contractile properties will be correlated to biochemical properties of individual muscle constituents of the motor unit; and 4) Enzyme characteristics will be determined in single fibers of human myopathies in which biochemical defects are suspected. The ultimate objective in furthering the understanding of neurotrophic interactions regulating muscle is to provide clues to the etiology of neuromuscular diseases demonstrating altered muscle metabolism.